Rivastigmine improves gait
disturbances in early study
LAST UPDATED 06.18.2015
Note that this
study was published as an abstract and presented at a conference. These data
and conclusions should be considered to be preliminary until published in a
peer-reviewed journal.
In a phase II,
randomized, double-blind, placebo-controlled trial involving 130 Parkinson's
patients who have fallen in the past year, the cholinesterase inhibitor
rivastigmine effectively reduced gait variability, a proxy for fall risk.
Adverse events were
generally mild and consistent with prior clinical experience.
Though rate of
falls was decreased with rivastigmine compared with placebo as a secondary
outcome measure, it remains to be seen whether this beneficial effect is borne
out in larger studies.
SAN DIEGO -- A cholinesterase
inhibitor improved gait in Parkinson's patients and may ultimately help
diminish falls in this population, researchers reported here.
In a phase II study, rivastigmine
(Exelon) improved gait variability during normal walking and during walking
while performing a simple cognitive task, Emily Henderson,
MRCP, MBChB, of the University of Bristol, reported at the Movement Disorders Society
meeting here.
It also reduced the rate of falls,
which was only a secondary endpoint in this study.
"This really just supports the
fact that we need to do a larger trial with falls as the primary endpoint to
see if this effect actually plays out in day-to-day life," Henderson told MedPage
Today.
Falls are a common problem in
Parkinson's disease, and Henderson said underlying cholinergic deficits
contribute to gait dysfunction and cognitive impairment -- both of which are
significant contributors to fall risk. These impairments only worsen as the
disease progresses, she added.
The researchers theorized that a
cholinesterase inhibitor may be able to mitigate those problems -- and, indeed,
a small study of the cholinesterase inhibitor donepezil (Aricept) found that to be
the case in 2010. This time, they assessed the effects of another
such agent, rivastigmine, which is already approved for the treatment of
Parkinson's dementia.
For their phase II, double-blind,
randomized, controlled trial, they enrolled 130 patients who'd had a fall in
the last year. These patients were randomized to either rivastigmine or
placebo, and the drug was uptitrated over 4 months to a maximum of 6 mg twice a
day, and then maintained at the highest tolerated dose for the next 4 months.
The primary outcome was step time
variability, a proxy marker for risk of falls, measured in three conditions:
normal walking, simple cognitive task, and complex cognitive task.
The study had a high retention rate
(95%), and the researchers performed an intention-to-treat analysis.
They found that in models adjusted
for factors including age, cognition, previous falls, rivastigmine improved
step time variability in two of the three walking conditions:
Normal walk: RR
0.72, 95% CI 0.58-0.88, P=0.002
Simple cognitive
task: RR 0.79, 95% CI 0.62-0.99, P=0.045
The findings were not significant for
the complex cognitive task, and Henderson noted that the "greatest
treatment effect was seen during normal walking."
There was no evidence of effect
modification by age group, cognition, or duration of Parkinson's disease, they
added.
For the secondary endpoints,
rivastigmine was associated with fewer falls per month (1.4 versus 2.4), and
there was a 29% relative reduction in the rate of falls with the drug.
Adverse events were consistent with
the literature and were predominantly mild and not related to trial medication,
Henderson said. Rivastigmine was associated with more occurrences of
gastrointestinal disturbance and urinary tract infection -- both of which are
known side effects of the drug.
The researchers concluded that while
rivastigmine improved gait variability, it remains to be seen whether that will
translate to a more clinically meaningful reduction in fall risk -- which needs
to be evaluated in future large-scale phase III trials.
Melissa
Nirenberg, MD, PhD, of NYU Langone Medical Center, who was not
involved in the study, said cholinesterase inhibitors for gait and falls in
Parkinson's is "a hot area of investigation."
"Multiple groups are looking at
this, and it would be novel if it works, but we don't know yet," Nirenberg
told MedPage Today. "Some people are trying it empirically.
Anecdotally, I haven't noticed any improvement in the gait of patients in whom
I start those drugs for cognitive impairment."
She added that currently, rehab and
safety precautions "are the main ways of averting falls. We don't have any
medications for this problem."
Novartis provided the study drug
plus placebo.
The researchers disclosed no
financial relationships with industry.
Reviewed
by Robert
Gross, MD Multiple Sclerosis Fellow, Corinne Goldsmith Dickinson
Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New
York, NY
Primary Source
International
Congress on Parkinson's Disease and Movement Disorders
Source Reference: Henderson EJ,
et al "The ReSPOnD trial: Rivastigmine to stabilize gait in Parkinson's
disease" MDS 2015; Abstract LBA10.
Staff Writer, MedPage Today
http://www.medpagetoday.com/MeetingCoverage/MDS/52166
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